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Abstract Online education remains challenging for many institutions of higher education (HE). COVID-19 lockdowns have demonstrated inequalities, underlining the need for more study on its effects on access and engagement. The recent I-TPACK model enables teachers to utilize technological resources to meet diverse learning needs, improve accessibility, and create engaging learning experiences for all students. Online inclusive learning environments (LEs) necessitate a comprehensive understanding of teacher and student needs and perspectives within HE, a level of education that is currently understudied. Moreover, in inclusive and online education, their voices are underrepresented in research and policy discussions, despite their importance. This study aims to investigate how teachers and students in HE articulate their preferred inclusive online LE and therefore adopted a qualitative research approach including homogeneous focus groups, directed by the I-TPACK model. Results present students’ and teachers’ key elements and conditions of an inclusive online LE. However, there is little preparation and common language on how to implement them. Online LEs’ inclusion potential is still underappreciated. This research provides policy suggestions closely aligned with practical application and highlights the necessity of venturing beyond the comfort zone exploring inclusive online practices, as presented by the I-TPACK model.

Purpose: Patients with chemotherapy-induced ovarian function failure (CIOFF) may experience ovarian function recovery (OFR). Earlier, we showed that OFR during treatment with anastrozole impacted the prognosis of hormone receptor-positive (HR+) breast cancer (BC) patients with CIOFF. Here, we present the long-term follow-up results. Methods: Postmenopausal women with HR+ BC who were 45–57 years of age and received chemotherapy were identified from the phase 3 DATA study (NCT00301457) on the extended use of anastrozole. Eligible patients were categorised into two groups: patients with CIOFF and definitely postmenopausal patients. Patients with CIOFF were monitored for OFR. Disease-free survival (DFS), distant recurrence-free survival (DRFS), and overall survival (OS) were compared between patients with OFR and patients without OFR using multivariable Cox regression analyses, including OFR as a time-dependent covariate. BC-specific mortality (BCSM) was compared between groups using the Fine and Gray method. Results: This study included 656 patients: 395 patients with CIOFF and 261 definitely postmenopausal patients. OFR occurred in 39 (12%) of 329 patients with CIOFF who were monitored for OFR. The median follow-up time was 13.3 years. Patients with OFR experienced a deterioration in DFS (hazard ratio (HR) = 1.54; 95% confidence interval (CI) 0.85–2.81), DRFS (HR = 1.51; 95% CI 0.73–3.11), OS (HR = 1.64; 95% CI 0.75–3.55), and BCSM (subdistribution HR = 1.98; 95% CI 0.84–4.63) when compared with patients without OFR. Conclusion: In patients with CIOFF, OFR during treatment with anastrozole was associated with a deterioration in BC outcomes. These findings underscore the importance of adequate ovarian function suppression in this subgroup of patients. [ABSTRACT FROM AUTHOR]

Purpose: In critically ill adults, withholding parenteral nutrition until 1 week after intensive care admission (Late-PN) facilitated recovery as compared with early supplementation of insufficient enteral nutrition with parenteral nutrition (Early-PN). However, the impact on long-term mortality and functional outcome, in relation to the estimated nutritional risk, remains unclear. Methods: In this prospective follow-up study of the multicenter EPaNIC randomized controlled trial, we investigated the impact of Late-PN on 2-year mortality (N = 4640) and physical functioning, assessed by the 36-Item Short Form Health Survey (SF-36; in 3292 survivors, responding 819 [738–1058] days post-randomization). To account for missing data, we repeated the analyses in two imputed models. To identify potential heterogeneity of treatment effects, we investigated the impact of Late-PN in different nutritional risk subgroups as defined by Nutritional Risk Screening-2002-score, modified NUTrition Risk in the Critically Ill-score, and age (above/below 70 years), and we evaluated whether there was statistically significant interaction between classification to a nutritional risk subgroup and the effect of the randomized intervention. Secondary outcomes were SF-36-derived physical and mental component scores (PCS & MCS). Results: Two-year mortality (20.5% in Late-PN, 19.8% in Early-PN; P = 0.54) and physical functioning (70 [40–90] in both study-arms; P = 0.99) were similar in both groups, also after imputation of missing physical functioning data. Likewise, Late-PN had no impact on 2-year mortality and physical functioning in any nutritional risk subgroup. PCS and MCS were similar in both groups. Conclusion: Late-PN did not alter 2-year survival and physical functioning in adult critically ill patients, independent of anticipated nutritional risk. [ABSTRACT FROM AUTHOR]

The development of superconducting qubit technology has shown great potential for the construction of practical quantum computers1,2. As the complexity of quantum processors continues to grow, the need for stringent fabrication tolerances becomes increasingly critical3. Utilizing advanced industrial fabrication processes could facilitate the necessary level of fabrication control to support the continued scaling of quantum processors. However, at present, these industrial processes are not optimized to produce high-coherence devices, nor are they a priori compatible with the approaches commonly used to make superconducting qubits. Here we demonstrate superconducting transmon qubits manufactured in a 300 mm complementary metal–oxide–semiconductor (CMOS) pilot line using industrial fabrication methods, with resulting relaxation and coherence times exceeding 100 μs. We show across-wafer, large-scale statistics of coherence, yield, variability and ageing that confirm the validity of our approach. The presented industry-scale fabrication process, which uses only optical lithography and reactive-ion etching, has a performance and yield in line with conventional laboratory-style techniques utilizing metal lift-off, angled evaporation and electron-beam writing4. Moreover, it offers the potential for further upscaling through three-dimensional integration5 and more process optimization. This result marks the advent of an alternative and new, large-scale, truly CMOS-compatible fabrication method for superconducting quantum computing processors.Superconducting transmon qubits have been fabricated in a 300 mm complementary metal–oxide–semiconductor (CMOS) pilot line using industrial fabrication methods, achieving relaxation and coherence times exceeding 100 μs. [ABSTRACT FROM AUTHOR]

Paradoxical reactions (PR) to tuberculosis (TB) treatment are common during treatment, but have also been described after treatment. A presentation with recurrent signs or symptoms of TB after cure or completion of prior treatment needs to be differentiated between microbiological relapse and a paradoxical reaction. We searched all published literature on post-treatment PR, and present a synthesis of 30 studies, focusing on the epidemiology, diagnosis and management of this phenomenon. We report an additional case vignette. The majority of studies were of lymph node TB (LN-TB), followed by central nervous system TB (CNS-TB). A total of 112 confirmed and 42 possible post-treatment PR cases were reported. The incidence ranged between 3 and 14% in LN-TB and was more frequent than relapses, and between 0 and 2% in all TB. We found four reports of pulmonary or pleural TB post-treatment PR cases. The incidence did not differ by length of treatment, but was associated with younger age at initial diagnosis, and having had a PR (later) during treatment. Post-treatment PR developed mainly within the first 6 months after the end of TB treatment but has been reported many years later (longest report 10 years). The mainstays of diagnosis and management are negative mycobacterial cultures and anti-inflammatory treatment, respectively. Due to the favourable prognosis in LN-TB recurrent symptoms, a short period of observation is warranted to assess for spontaneous regression. In CNS-TB with recurrent symptoms, immediate investigation and anti-inflammatory treatment with the possibility of TB retreatment should be undertaken. [ABSTRACT FROM AUTHOR]

During the first postoperative days following minimally invasive sacroiliac joint fusion (MISJF), patients often report serious pain, which contributes to high utilization of painkillers and prevention of early mobilization. This prospective, double-blind randomized controlled trial investigates the effectiveness of intraoperative SIJ infiltration with bupivacaine 0.50% versus placebo (NaCl 0.9%) in 42 patients in reducing postoperative pain after MISJF. The primary outcome was difference in pain between bupivacaine and placebo groups, assessed as fixed factor in a linear mixed model. Secondary outcomes were opioid consumption, patient satisfaction, adverse events, and length of hospital stay. We found that SIJ infiltration with bupivacaine did not affect postoperative pain scores in comparison with placebo, neither as group-effect (p = 0.68), nor dependent on time (group*time: p = 0.87). None of the secondary outcome parameters were affected in the postoperative period in comparison with placebo, including opioid consumption (p = 0.81). To conclude, intra-articular infiltration of the SIJ with bupivacaine at the end of MISJF surgery is not effective in reducing postoperative pain. Hence, we do not recommend routine use of intraoperative SIJ infiltration with analgesia in MISJF. [ABSTRACT FROM AUTHOR]

Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival in patients with Stage III ovarian cancer following interval cytoreductive surgery (CRS). Optimising patient selection is essential to maximise treatment efficacy and avoid overtreatment. This study aimed to identify biomarkers that predict HIPEC benefit by analysing gene signatures and cellular composition of tumours from participants in the OVHIPEC-1 trial. Methods: Whole-transcriptome RNA sequencing data were retrieved from high-grade serous ovarian cancer (HGSOC) samples from 147 patients obtained during interval CRS. We performed differential gene expression analysis and applied deconvolution methods to estimate cell-type proportions in bulk mRNA data, validated by histological assessment. We tested the interaction between treatment and potential predictors on progression-free survival using Cox proportional hazards models. Results: While differential gene expression analysis did not yield any predictive biomarkers, the cellular composition, as characterised by deconvolution, indicated that the absence of macrophages and the presence of B cells in the tumour microenvironment are potential predictors of HIPEC benefit. The histological assessment confirmed the predictive value of macrophage absence. Conclusion: Immune cell composition, in particular macrophages absence, may predict response to HIPEC in HGSOC and these hypothesis-generating findings warrant further investigation. Clinical trial registration: NCT00426257. [ABSTRACT FROM AUTHOR]

This study investigated the effects of dietary supplements, citrus (CTS) and cucumber (CMB), on the jejunum and cecum microbiota of 14- and 28-days old broiler chickens to evaluate their impact on the gut health and assess their role as alternatives to antibiotic growth promoters (ABGPs). 16SrRNA gene sequencing revealed the overall bacterial microbiota composition was significantly affected by the gut site (p?

Purpose: The optimal duration of immobilization for the conservative treatment of non- or minimally displaced and displaced distal radius fractures remains under debate. This research aims to review studies of these treatments to add evidence regarding the optimal immobilization period. Methods: A comprehensive database search was conducted. Studies investigating and comparing short (< 3 weeks) versus long (> 3 weeks) immobilizations for the conservative treatment of distal radius fractures were included. The studies were evaluated for radiological and functional outcomes, including pain, grip strength, and range of motion. Two reviewers independently reviewed all studies and performed the data extraction. Results: The initial database search identified 11.981 studies, of which 16 (involving 1.118 patients) were ultimately included. Patient-reported outcome measurements, grip strength, range of motion, and radiological outcomes were often better after shorter immobilization treatments. Radiological outcomes were better with longer immobilization in two studies and shorter immobilization in one study. Fourteen studies concluded that early mobilization is preferred, while the remaining two studies observed better outcomes with longer immobilization. The data were unsuitable for meta-analysis due to their heterogeneous nature. Conclusion: Shorter immobilization for conservatively treated distal radius fractures often yield equal or better outcomes than longer immobilizations. The immobilization for non- or minimally displaced distal radius fractures could therefore be shortened to 3 weeks or less. Displaced and reduced distal radius fractures cannot be immobilized shorter than 4 weeks due to the risk of complications. Future research with homogeneous groups could elucidate the optimal duration of immobilization. [ABSTRACT FROM AUTHOR]

Online education remains challenging for many institutions of higher education (HE). COVID-19 lockdowns have demonstrated inequalities, underlining the need for more study on its effects on access and engagement. The recent I-TPACK model enables teachers to utilize technological resources to meet diverse learning needs, improve accessibility, and create engaging learning experiences for all students. Online inclusive learning environments (LEs) necessitate a comprehensive understanding of teacher and student needs and perspectives within HE, a level of education that is currently understudied. Moreover, in inclusive and online education, their voices are underrepresented in research and policy discussions, despite their importance. This study aims to investigate how teachers and students in HE articulate their preferred inclusive online LE and therefore adopted a qualitative research approach including homogeneous focus groups, directed by the I-TPACK model. Results present students' and teachers' key elements and conditions of an inclusive online LE. However, there is little preparation and common language on how to implement them. Online LEs' inclusion potential is still underappreciated. This research provides policy suggestions closely aligned with practical application and highlights the necessity of venturing beyond the comfort zone exploring inclusive online practices, as presented by the I-TPACK model. [ABSTRACT FROM AUTHOR]

Ameloblasts are the specialized dental epithelial cell type responsible for enamel formation. Following completion of enamel development in humans, ameloblasts are lost and biological repair or regeneration of enamel is not possible. In the past, in vitro models to study dental epithelium and ameloblast biology were limited to freshly isolated primary cells or immortalized cell lines, both with limited translational potential. In recent years, large strides have been made with the development of induced pluripotent stem cell and organoid models of this essential dental lineage – both enabling modeling of human dental epithelium. Upon induction with several different signaling factors (such as transforming growth factor and bone morphogenetic proteins) these models display elevated expression of ameloblast markers and enamel matrix proteins. The advent of 3D bioprinting, and its potential combination with these advanced cellular tools, is poised to revolutionize the field – and its potential for tissue engineering, regenerative and personalized medicine. As the advancements in these technologies are rapidly evolving, we evaluate the current state-of-the-art regarding in vitro cell culture models of dental epithelium and ameloblast lineage with a particular focus toward their applicability for translational tissue engineering and regenerative/personalized medicine. Future perspectives for in vitro modeling of dental epithelium and ameloblasts. Development of iPSC and organoid models that can reliably generate dental epithelium and ameloblast-like cells, together with advances in 3D bioprinting, provide promising tools for enamel research. Advanced models will provide new avenues for development of enamel repair/regeneration approaches, for testing of dental materials or drugs, studying host-pathogen and/or cell-cell interactions, in vitro modeling of enamel diseases (e.g. amelogenesis imperfecta) and developing novel insights in fundamental tooth biology (e.g. regulation of amelogenesis, lineage specification). Abbreviations: iPSC: induced pluripotent stem cells; TO: tooth organoids; DE: dental epithelium; AB: ameloblast. [ABSTRACT FROM AUTHOR]

Background and Objective: The interstitial fluid of tissues is the effect site for antibiotics targeting extracellular pathogens. Microdialysis studies investigating these concentrations in muscle and subcutaneous tissue have reported notable variability in tissue penetration. This study aimed to comprehensively summarise the existing data on interstitial fluid penetration in these tissues and to identify potential factors influencing antibiotic distribution. Methods: A literature review was conducted, focusing on subcutaneous and intramuscular microdialysis studies of antibiotics in both adult healthy volunteers and patients. Random-effect meta-analyses were used to aggregate effect size estimates of tissue penetration. The primary parameter of interest was the unbound penetration ratio, which represents the ratio of the area under the concentration–time curve in interstitial fluid relative to the area under the concentration–time curve in plasma, using unbound concentrations. Results: In total, 52 reports were incorporated into this analysis. The unbound antibiotic exposure in the interstitial fluid of healthy volunteers was, on average, 22% lower than in plasma. The unbound penetration ratio values were higher after multiple dosing but did not significantly differ between muscle and subcutaneous tissue. Unbound penetration ratio values were lower for acids and bases compared with neutral antibiotics. Neither the molecular weight nor the logP of the antibiotics accounted for the variations in the unbound penetration ratio. Obesity was associated with lower interstitial fluid penetration. Conditions such as sepsis, tissue inflammation and tissue ischaemia were not significantly associated with altered interstitial fluid penetration. Conclusions: This study highlights the variability and generally lower exposure of unbound antibiotics in the subcutaneous and intramuscular interstitial fluid compared with exposure in plasma. Future research should focus on understanding the therapeutic relevance of these differences and identify key covariates that may influence them. [ABSTRACT FROM AUTHOR]

Objectives: Tooth extraction is one of the most frequently performed medical procedures. The indication is based on the combination of clinical and radiological examination and individual patient parameters and should be made with great care. However, determining whether a tooth should be extracted is not always a straightforward decision. Moreover, visual and cognitive pitfalls in the analysis of radiographs may lead to incorrect decisions. Artificial intelligence (AI) could be used as a decision support tool to provide a score of tooth extractability. Material and methods: Using 26,956 single teeth images from 1,184 panoramic radiographs (PANs), we trained a ResNet50 network to classify teeth as either extraction-worthy or preservable. For this purpose, teeth were cropped with different margins from PANs and annotated. The usefulness of the AI-based classification as well that of dentists was evaluated on a test dataset. In addition, the explainability of the best AI model was visualized via a class activation mapping using CAMERAS. Results: The ROC-AUC for the best AI model to discriminate teeth worthy of preservation was 0.901 with 2% margin on dental images. In contrast, the average ROC-AUC for dentists was only 0.797. With a 19.1% tooth extractions prevalence, the AI model's PR-AUC was 0.749, while the dentist evaluation only reached 0.589. Conclusion: AI models outperform dentists/specialists in predicting tooth extraction based solely on X-ray images, while the AI performance improves with increasing contextual information. Clinical relevance: AI could help monitor at-risk teeth and reduce errors in indications for extractions. [ABSTRACT FROM AUTHOR]

Purpose: The need for an interval between the administration of long-acting Somatostatin Receptor Analogues (SSA) and the [68Ga]Ga-DOTA-TATE PET has been questioned based on recent literature in the new EANM guidelines. Here an earlier studies showed that SSA injection immediately before SSTR PET had minimal effect on normal organ and tumor uptake (1). However, data are scarce and there are (small) differences between [68Ga]Ga-DOTA-TATE and [68Ga]Ga-DOTA-TOC binding affinity, and it remains unknown whether these findings can be directly translated to scans with [68Ga]Ga-DOTA-TOC as well. The purpose of this study was to assess the effect of SSA use on the biodistribution in a subsequent [68Ga]Ga-DOTA-TOC PET/CT and compare this intra-individually across several cycles of SSA treatments. Methods: Retrospectively, 35 patients with NENs were included. [68Ga]Ga-DOTA-TOC PET at staging and after the 1st and 2nd cycle of SSA were included. SUVmean and SUVmax of blood, visceral organs, primary tumor and two metastases were determined. Also, the interval between SSA therapy and the PET scan was registered. Results: Treatment with SSA resulted in a significantly higher bloodpool activity and lower visceral tracer uptake. This effect was maintained after a 2nd cycle of SSA therapy. Furthermore, there was an inverse relationship between bloodpool tracer availability and visceral tracer binding and a positive correlation between bloodpool tracer availability and primary tumor tracer uptake. With an interval of up to 5 days, there was a significantly higher bloodpool activity than at longer intervals. Conclusion: Absolute comparison of the SUV on [68Ga]Ga-DOTA-TOC PET should be done with caution as the altered biodistribution of the tracer after SSA treatment should be taken into account. We recommend not to perform a scan within the first 5 days after the injection of lanreotide. [ABSTRACT FROM AUTHOR]

Background: Previous reports have provided (some) demographics of the cosmetic consumer; however, findings are not unequivocal. This relates to differences in the studies' categorizations, samples, and contextual factors. Methods: Employing a cross-sectional survey design, which was disseminated by 11 cosmetic clinics and consumer platforms in the Netherlands, this study provides a clear overview of a total of 734 Dutch cosmetic consumers' (a) demographic characteristics; (b) motivations for undergoing a range of specific cosmetic procedures; (c) cosmetic procedure frequency, i.e., how frequently they undergo particular procedures; and (d) frequency of, and motivations for, switching clinics. Relations between cosmetic consumers' demographics, motivations for cosmetic procedures, and different procedures chosen were also established. Results: There is no unequivocal characterization of 'the' cosmetic consumer in the Netherlands, although they mostly identified as heterosexual women from Dutch descent with relatively high educational attainment levels and a high income. Some regional differences in terms of cosmetic procedure engagement were observed. Motivations for cosmetic procedure engagement were multifaceted, and responses varied between open- and closed-ended questions. Few relations between predictors and (a selection of) cosmetic procedures proved significant. (Higher) age and high educational attainment positively correlated with undergoing botulinum toxin injections and eyelid corrections. Gender and daily use of highly visual social media positively correlated with undergoing dermal filler injections. Lastly, lower-educated consumers were significantly more likely to have breast enlargements than higher-educated consumers. Conclusions: This study provides a comprehensive overview of the demographic characteristics and motivations of a varied sample of cosmetic consumers, and the types and quantities of cosmetic procedures they undergo. In terms of demographics, we can conclude that there is no unequivocal characterization of 'the' cosmetic consumer in the Netherlands, although she frequently identifies as a heterosexual female of Dutch descent. Level of Evidence: Not gradable [ABSTRACT FROM AUTHOR]

Due to their exceptional solubility and stability, nanobodies have emerged as powerful building blocks for research tools and therapeutics. However, their generation in llamas is cumbersome and costly. Here, by inserting an engineered llama immunoglobulin heavy chain (IgH) locus into IgH-deficient mice, we generate a transgenic mouse line, which we refer to as 'LamaMouse'. We demonstrate that LamaMice solely express llama IgH molecules without association to Igκ or λ light chains. Immunization of LamaMice with AAV8, the receptor-binding domain of the SARS-CoV-2 spike protein, IgE, IgG2c, and CLEC9A enabled us to readily select respective target-specific nanobodies using classical hybridoma and phage display technologies, single B cell screening, and direct cloning of the nanobody-repertoire into a mammalian expression vector. Our work shows that the LamaMouse represents a flexible and broadly applicable platform for a facilitated selection of target-specific nanobodies. Nanobodies are normally made from immunized camelids, Ig transgenic mice or synthetic libraries. In this study, the authors introduce the llama Ig heavy chain locus into mice lacking this locus, thereby generating a line in which nanobodies can be made by direct immunization in the absence of an endogenous antibody repertoire. [ABSTRACT FROM AUTHOR]

The Malabo Declaration places the transformation of agriculture and food systems at the centre of regional and national policy priorities across Africa. Transformative change in the way that food is produced, processed and consumed is seen as not only necessary for addressing the complex challenges of food security and poverty alleviation, but also as a driver of new employment opportunities and economic development. As pointed out within the recent UN Food Systems Summit, essential elements of food system transformations include digital transitions and the empowerment of women and youth. However, there are few empirical examples demonstrating how these agendas come together to affect food system change. Here we focus on an enterprising group of young farmers referred to as Malawi's new achikumbe elite, who are urban based, educated and engaging in agriculture on a commercial basis. The aim is to characterise this emergent group of agriculturalists and to understand the role that they have within the transformation of Malawi-s agricultural sector. We explore how digital platforms are supporting the emergence of this new category of farmer and positioning young people as agents of change in food systems transformation. Based on interviews and ethnographic research with 32 young farmers between 2018 and 2022 combined with interviews with representatives of service providers and agricultural organisations, we argue that this group is characterised by a higher level of education, self-dependency and use of digital platforms, enabling them to adapt their context to sourcing production resources and engaging in commercial agriculture. We present evidence that digital platforms are supporting the new achikumbe elite (NAE) to engage flexibly with new commercial markets, contracts and access a wider range of training and advice. However, while digital platforms can offer more equitable access to information and market opportunities, they also represent potential avenues for food system transformations that are inequitable. As such, we argue that there is need for digital technologies to mitigate against potential inequalities. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae releases the peptides AKTIKITQTR and FNEMQPIVDRQ, which bind the pneumococcal proteins AmiA and AliA respectively, two substrate-binding proteins of the ABC transporter Ami-AliA/AliB oligopeptide permease. Exposure to these peptides alters pneumococcal phenotypes such as growth. Using a mutant in which a permease domain of the transporter was disrupted, by growth analysis and epifluorescence microscopy, we confirmed peptide uptake via the Ami permease and intracellular location in the pneumococcus. By RNA-sequencing we found that the peptides modulated expression of genes involved in metabolism, as pathways affected were mostly associated with energy or synthesis and transport of amino acids. Both peptides downregulated expression of genes involved in branched-chain amino acid metabolism and the Ami permease; and upregulated fatty acid biosynthesis genes but differed in their regulation of genes involved in purine and pyrimidine biosynthesis. The transcriptomic changes are consistent with growth suppression by peptide treatment. The peptides inhibited growth of pneumococcal isolates of serotypes 3, 8, 9N, 12F and 19A, currently prevalent in Switzerland, and caused no detectable toxic effect to primary human airway epithelial cells. We conclude that pneumococci take up K. pneumoniae peptides from the environment via binding and transport through the Ami permease. This changes gene expression resulting in altered phenotypes, particularly reduced growth. [ABSTRACT FROM AUTHOR]

Purpose: Comorbid insomnia often occurs in patients with obstructive sleep apnea (OSA), referred to as COMISA. Cortical arousals manifest as a common feature in both OSA and insomnia, often accompanied by elevated heart rate (HR). Our objective was to evaluate the heart rate response to nocturnal cortical arousals in patients with COMISA and patients with OSA alone. Methods: We analyzed data from patients with COMISA and from patients with OSA matched for apnea-hypopnea index. Sleep staging and analysis of respiratory events and cortical arousals were performed using the Philips Somnolyzer automatic scoring system. Beat-by-beat HR was analyzed from the onset of the cortical arousal to 30 heartbeats afterwards. HR responses were divided into peak and recovery phases. Cortical arousals were separately evaluated according to subtype (related to respiratory events and spontaneous) and duration (3–6 s, 6–10 s, 10–15 s). Results: A total of 72 patients with COMISA and 72 patients with OSA were included in this study. There were no overall group differences in the number of cortical arousals with and without autonomic activation. No significant differences were found for spontaneous cortical arousals. The OSA group had more cortical arousals related to respiratory events (21.0 [14.8–30.0] vs 16.0 [9.0–27.0], p = 0.016). However, the COMISA group had longer cortical arousals (7.2 [6.4–7.8] vs 6.7 [6.2–7.7] s, p = 0.024) and the HR recovery phase was prolonged (52.5 [30.8–82.5] vs 40.0 [21.8–55.5] beats/min, p = 0.017). Both the peak and the recovery phase for longer cortical arousals with a duration of 10–15 s were significantly higher in patients with COMISA compared to patients with OSA (47.0 [27.0–97.5] vs 34.0 [21.0–71.0] beats/min, p = 0.032 and 87.0 [47.0–132.0] vs 71.0 [43.0–103.5] beats/min, p = 0.049, respectively). Conclusions: The HR recovery phase after cortical arousals related to respiratory events is prolonged in patients with COMISA compared to patients with OSA alone. This response could be indicative of the insomnia component in COMISA. [ABSTRACT FROM AUTHOR]

Background and Objective: Haemophilia B is a rare genetic disease that is caused by a deficiency of coagulation factor IX (FIX) in the blood and leads to internal and external bleeding. Under the current standard of care, haemophilia is treated either prophylactically or on-demand via intravenous infusions of FIX. These treatment strategies impose a high burden on patients and health care systems as haemophilia B requires lifelong treatment, and FIX is costly. Etranacogene dezaparvovec (ED) is a gene therapy for haemophilia B that has been recently approved by the United States Food and Drug Administration and has received a recommendation for conditional marketing authorization by the European Medicines Agency. We aimed to examine the cost-effectiveness of ED versus extended half-life FIX (EHL-FIX) prophylaxis for moderate-to-severe haemophilia B from a German health care payer perspective. Methods: A microsimulation model was implemented in R. The model used data from the ED phase 3 clinical trial publication and further secondary data sources to simulate and compare patients receiving ED or EHL-FIX prophylaxis over a lifetime horizon, with the potential for ED patients to switch treatment to EHL-FIX prophylaxis when the effectiveness of ED waned. Primary outcomes of this analysis included discounted total costs, discounted quality-adjusted life years (QALYs), incremental cost-effectiveness, and the incremental net monetary benefit. The annual discount rate for costs and effects was 3%. Uncertainty was examined via probabilistic analysis and additional univariate sensitivity analyses. Results: Probabilistic analysis indicated that patients treated with ED instead of EHL-FIX prophylaxis gained 0.50 QALYs and experienced cost savings of EUR 1,179,829 at a price of EUR 1,500,000 per ED treatment. ED was the dominant treatment strategy. At a willingness to pay of EUR 50,000/QALY, the incremental net monetary benefit amounted to EUR 1,204,840. Discussion: Depending on the price, ED can save costs and improve health outcomes of haemophilia patients compared with EHL-FIX prophylaxis, making it a potentially cost-effective alternative. These results are uncertain due to a lack of evidence regarding the long-term effectiveness of ED. [ABSTRACT FROM AUTHOR]

Preterm neonates are at risk of long-term neurodevelopmental impairments due to disruption of natural brain development. Electroencephalography (EEG) analysis can provide insights into brain development of preterm neonates. This study aims to explore the use of microstate (MS) analysis to evaluate global brain dynamics changes during maturation in preterm neonates with normal neurodevelopmental outcome. The dataset included 135 EEGs obtained from 48 neonates at varying postmenstrual ages (26.4 to 47.7 weeks), divided into four age groups. For each recording we extracted a 5-minute epoch during quiet sleep (QS) and during non-quiet sleep (NQS), resulting in eight groups (4 age group x 2 sleep states). We compared MS maps and corresponding (map-specific) MS metrics across groups using group-level maps. Additionally, we investigated individual map metrics. Four group-level MS maps accounted for approximately 70% of the global variance and showed non-random syntax. MS topographies and transitions changed significantly when neonates reached 37 weeks. For both sleep states and all MS maps, MS duration decreased and occurrence increased with age. The same relationships were found using individual maps, showing strong correlations (Pearson coefficients up to 0.74) between individual map metrics and post-menstrual age. Moreover, the Hurst exponent of the individual MS sequence decreased with age. The observed changes in MS metrics with age might reflect the development of the preterm brain, which is characterized by formation of neural networks. Therefore, MS analysis is a promising tool for monitoring preterm neonatal brain maturation, while our study can serve as a valuable reference for investigating EEGs of neonates with abnormal neurodevelopmental outcomes. [ABSTRACT FROM AUTHOR]

Background and Objective: Drug dosing should ideally be based on the drug concentrations at the target site, which, for most drugs, corresponds to the tissue. The exact influence of growth and development on drug tissue distribution is unclear. This systematic review compiles the current knowledge on the tissue distribution of systemically applied drugs in children, with the aim to identify priorities in tissue pharmacokinetic (PK) research in this population. Methods: A systematic literature search was performed in the MEDLINE and Embase databases. Results: Forty-two relevant articles were identified, of which 71% investigated antibiotics, while drug classes from the other studies were anticancer drugs, antifungals, anthelmintics, sedatives, thyreostatics, immunomodulators, antiarrhythmics, and exon skipping therapy. The majority of studies (83%) applied tissue biopsy as the sampling technique. Tonsil and/or adenoid tissue was most frequently examined (70% of all included patients). The majority of studies had a small sample size (median 9, range 1–93), did not include the youngest age categories (neonates and infants), and were of low reporting quality. Due to the heterogeneous data from different study compounds, dosing schedules, populations, and target tissues, the possibility for comparison of PK data between studies was limited. Conclusion: The influence of growth and development on drug tissue distribution continues to be a knowledge gap, due to the paucity of tissue PK data in children, especially in the younger age categories. Future research in this field should be encouraged as techniques to safely investigate drug tissue disposition in children are available. [ABSTRACT FROM AUTHOR]

Aim: To evaluate changes in healthcare utilisation and comprehensive packages of care activities and procedures (referred in the Netherlands to as 'diagnose-behandelcombinatie (DBC) care products) during the implementation of the TeleCheck-AF approach (teleconsultation supported by app-based heart rate/rhythm monitoring) in a Dutch atrial fibrillation (AF) clinic. Methods and results: In the Maastricht University Medical Centre+ AF Clinic, data on healthcare utilisation and DBC care products for patients consulted by both a conventional approach in 2019 and the TeleCheck-AF approach in 2020 were analysed. A patient experience survey was performed. Thirty-seven patients (median age 68 years; 40% women) were analysed. With the conventional approach, 35 face-to-face consultations and 0 teleconsultations were conducted. After the implementation of TeleCheck-AF, the number of face-to-face consultations dropped by 80% (p < 0.001) and teleconsultations increased to 45 (p < 0.001). While 42 electrocardiograms (ECGs) and 25 Holter ECGs or echocardiograms were recorded when using the conventional approach, the number of ECGs decreased by 71% (p < 0.001) and Holter ECGs or echocardiograms by 72% (p < 0.001) with the TeleCheck-AF approach. The emergency department patient presentations showed no statistically significant change (p = 0.33). Overall, 57% of medium-weight DBC care products were changed to light-weight ones during implementation of the TeleCheck-AF approach. Patient satisfaction with the TeleCheck-AF approach was high. Conclusion: The implementation of TeleCheck-AF led to a change in healthcare utilisation, a change from medium-weight to light-weight DBC care products and a reduction in patient burden. These results created the basis for a new reimbursement code for the TeleCheck-AF approach in the Netherlands. [ABSTRACT FROM AUTHOR]

Purpose: Radiological extranodal extension (rENE) is a well-known negative prognosticator in head and neck squamous cell carcinoma (HNSCC). However, controversy remains regarding the prognostic effect of rENE in HPV-positive oropharyngeal SCCs (OPSCC). This single-center retrospective cohort analysis assessed the prognostic role of rENE in an HPV + OPSCC population and tried to validate a recently proposed modification of the TNM8 N-classification. Methods: 129 patients with HPV + OPSCC, of whom 106 cN + patients, were included. Radiological imaging (CT, MRI or both) was reanalyzed by a senior head and neck radiologist. Overall survival (OS), disease-free survival (DFS), locoregional recurrence-free survival (LRFS), and disease-specific survival (DSS) were evaluated. Cox proportional hazard models were used for estimating hazard ratios (HR). Results: A non-significant trend towards better outcomes in the rENE– group, as compared to the rENE + population, was observed for 5 year OS [80.99% vs 68.70%, HR: 2.05, p = 0.160], 5 year RFS [78.81% vs 67.87%, HR: 1.91, p = 0.165], 5 year DFS [77.06% vs 60.16%, HR: 2.12, p = 0.0824] and 5 year DSS [88.83% vs 81.93%, HR: 2.09, p = 0.195]. OS declined with ascending levels of rENE (p = 0.020). Multivariate analysis identified cT-classification and smoking as independent negative predictors for OS/DFS. The proposed modification of the TNM8 N-classification could not be validated. Conclusions: Although rENE could not be identified as an independent negative prognosticator for outcome in our HPV + OPSCC population, outcomes tend to deteriorate with increasing rENE. [ABSTRACT FROM AUTHOR]

Titanium silicates of MWW structures with different Si/Ti ratios were prepared via hydrothermal synthesis using piperidine as the structure directing agent and boric acid as the crystallization agent. All the syntheses resulted in highly crystalline materials independent of the Si/Ti ratio. The observed morphology showed MWW-like well-defined thin hexagonal platelets. The synthesized Ti-MWW materials exhibited higher surface areas and partial meso-porosity compared to the commercial TS-1 catalyst. The coordination of the Ti-species was investigated by UV–vis- and IR-spectroscopy. The MWW titanium silicates were tested for the catalytic performance in the epoxidation of propylene in a laboratory-scale trickle bed reactor to compare their clear different physico-chemical properties with the commercial TS-1. The synthesized Ti-MWW materials showed significantly higher catalytic activities, up to 3.5 times, using acetonitrile as the solvent and enhanced epoxide selectivities partially up to 100% in methanol unlike TS-1. The effect of the Ti content in the MWW and the calcination conditions were investigated in propylene epoxidation, revealing the beneficial effect of a lower calcination temperature and an increased Ti content on the activity. The catalytic results were correlated with the physico-chemical properties of the synthesized materials. [ABSTRACT FROM AUTHOR]

Background: In patients treated for head and neck cancer, imaging studies are usually obtained within 3–6 months after treatment for assessment of treatment response. After 6 months, most guidelines advocate clinical follow-up, with imaging reserved for patients with clinically suspect or equivocal findings. However, some guidelines do recommend systematic imaging surveillance, and many clinicians tend to include some type of imaging in their follow-up schemes. Objectives: This systematic review focuses on the usefulness of routine (systematic) post-treatment imaging surveillance of head and neck cancer beyond the first 3–6-month baseline imaging study. Methods: A systematic literature search was conducted using PubMed and Google Scholar. Additional studies were identified by reviewing reference lists. Only original studies and review papers were considered. Results obtained with systematic post-treatment surveillance imaging were compared to symptom-directed imaging and/or clinical finding-directed imaging. Results: Five hundred twenty-one records were identified through the database search, and 44 additional records were identified through other sources. Forty-eight articles were selected for the final review. Analysis of these records showed that almost half of cases of locoregional recurrences and/or metastases were only detected by imaging (40.9%), and the mean time of detection of recurrent or metastatic disease (11.5 months) was well beyond the period of the first post-treatment scan. Most authors reported superior results with PET-CT when compared to other imaging techniques. Conclusion: Strong arguments were found in favor of systematic imaging surveillance in locoregional advanced head and neck cancer during at least one and preferably 2 years after treatment. Critical relevance statement: Analysis of the selected records showed that almost half of cases of locoregional recurrences and/or metastases were only detected by imaging. This systematic review suggests that imaging may currently be underused in the post-treatment surveillance of patients with head and neck cancer. Key points: • This systematic review focuses on the usefulness of long-term systematic imaging surveillance in patients treated for head and neck cancer. • Analysis of 521 articles revealed that systematic imaging allowed the initial detection of locoregional recurrences and/or metastases in more than 40% of patients. • Imaging may currently be underused in the post-treatment surveillance of patients with advanced head and neck cancer. [ABSTRACT FROM AUTHOR]

Purpose: In this systematic review, we evaluate the effect of radiographs and 2D and 3D imaging techniques on the interobserver agreement of six commonly used classification systems for tibial plateau fractures. Methods: In accordance with PRISMA guidelines, PubMed, Cochrane, Embase and Web of Science were searched for studies regarding the effect of 2D and 3D imaging techniques on the interobserver agreement of tibial plateau classification systems. Studies validating new classification systems, not providing own data or only providing information on the interobserver agreement for radiographs were excluded. Studies were scored based on the ROBINS-I risk of bias tool. Results: Our review analysed 14 studies on different classification systems used for tibial plateau fractures in clinical practice, with the Schatzker classification being the most commonly used classification system. The results showed that the addition of 2D CT led to a significant improvement of interobserver agreement for one study. However, other included studies showed varying levels of interobserver agreement, ranging from fair to substantial according to the interpretation by Landis and Koch. The addition of 3D CT resulted in a significant deterioration in one study for the Schatzker classification. Similar to the addition of 2D CT, the interobserver agreement for the Schatzker classification with the addition of 3D CT were heterogeneous ranging from fair to almost perfect according to the interpretation by Landis and Koch. Conclusions: The use of 2D CT can be recommended for classifying tibial plateau fractures with the Schatzker classification, AO/OTA classification and Hohl classification. The value of 3D CT on the interobserver agreement of commonly used classification systems remains uncertain and unproven. Therefore, we do not recommend the use of 3D CT for the classification of tibial plateau fractures. Overall, the advancement of imaging techniques is not in line with the advancement in interobserver agreement on fracture classification. [ABSTRACT FROM AUTHOR]

This article uses the latest Spanish Survey on Homeless People to address whether traumatic experiences, sociodemographic characteristics, and homeless categories are associated with being an abstainer, a risky drinker, or a high-risk drinker. The sample was composed of 3,407 Spanish homeless adults ranging from 18 to 93 years old (Mage = 41.30, SD = 13.86). A multinomial logistic regression model was used. Results showed that experiencing childhood problems and demographic factors, such as being male, single, over 50, living in insecure or inadequate housing, and having lived in a shelter for less than three months were associated with alcohol consumption. Likewise, traumatic life events, such as a parent having been in prison, illness, disabilities, and alcohol problems in the family or themselves, are also risk factors in alcohol use. The findings from Spain support that early intervention strategies both disrupt cumulative inequality and empower those at risk of homelessness to develop their skills and improve their wellbeing. [ABSTRACT FROM AUTHOR]

A two-step strategy combining assisted benchmark testing (entry controls) and External Quality Assessments (EQAs) with blinded simulated clinical specimens to enhance and maintain the quality of nucleic acid amplification testing was developed. This strategy was successfully applied to 71 diagnostic laboratories in The Netherlands when upscaling the national diagnostic capacity during the SARS-CoV-2 pandemic. The availability of benchmark testing in combination with advice for improvement substantially enhanced the quality of the laboratory testing procedures for SARS-CoV-2 detection. The three subsequent EQA rounds demonstrated high quality testing with regard to specificity (99.6% correctly identified) and sensitivity (93.3% correctly identified). Even with the implementation of novel assays, changing workflows using diverse equipment and a high degree of assay heterogeneity, the overall high quality was maintained using this two-step strategy. We show that in contrast to the limited value of Cq value for absolute proxies of viral load, these Cq values can, in combination with metadata on strategies and techniques, provide valuable information for laboratories to improve their procedures. In conclusion, our two-step strategy (preparation phase followed by a series of EQAs) is a rapid and flexible system capable of scaling, improving, and maintaining high quality diagnostics even in a rapidly evolving (e.g. pandemic) situation. [ABSTRACT FROM AUTHOR]

Objectives: To determine a data-based optimal annual radical cystectomy (RC) hospital volume threshold and evaluate its clinical significance regarding perioperative mortality, complications, length of hospital stay, and hospital revenues. Material and methods: We used the German Nationwide inpatient Data, provided by the Research Data Center of the Federal Bureau of Statistics (2005–2020). 95,841 patients undergoing RC were included. Based on ROC analyses, the optimal RC threshold to reduce mortality, ileus, sepsis, transfusion, hospital stay, and costs is 54, 50, 44, 44, 71 and 76 cases/year, respectively. Therefore, we defined an optimal annual hospital threshold of 50 RCs/year, and we also used the threshold of 20 RCs/year proposed by the EAU guidelines to perform multiple patient-level analyses. Results: 28,291 (29.5%) patients were operated in low- (< 20 RC/year), 49,616 (51.8%) in intermediate- (20–49 RC/year), and 17,934 (18.7%) in high-volume (≥ 50 RC/year) centers. After adjusting for major risk factors, high-volume centers were associated with lower inpatient mortality (OR 0.72, 95% CI 0.64–0.8, p < 0.001), shorter length of hospital stay (2.7 days, 95% CI 2.4–2.9, p < 0.001) and lower costs (457 Euros, 95% CI 207–707, p < 0.001) compared to low-volume centers. Patients operated in low-volume centers developed more perioperative complications such as transfusion, sepsis, and ileus. Conclusions: Centralization of RC not only improves inpatient morbidity and mortality but also reduces hospital stay and costs. We propose a threshold of 50 RCs/year for optimal outcomes. [ABSTRACT FROM AUTHOR]

Purpose: The current rehabilitation for patients with surgically treated displaced intra-articular calcaneal fractures (DIACFs) consists of non-weightbearing for 8–12 weeks. The purpose of the present survey was to investigate the current pre-, peri- and post-operative practices among Dutch foot and ankle surgeons. Moreover, it aims to analyze whether surgeons comply to the Arbeitsgemeinschaft für Osteosynthesefragen (AO) guidelines and which decision criteria were used in the determination of the start of weightbearing. Methods: A survey was distributed among Dutch trauma and orthopaedic surgeons to determine the most common practices in postoperative weightbearing in patients with DIACFs. Results: 75 surgeons responded to the survey. 33% of the respondents adhered to the AO guidelines. 4% of the respondents strictly followed non-weightbearing guidelines, while 96% interpret the AO guidelines or their local protocol freely, in any frequency. When respondents tended to deviate from the AO guidelines or local protocol, a good patients' compliance to therapy was expected. 83% of the respondents started weightbearing on the fracture, based on reported patient complaints. 87% of the respondents did not see any relation between early weightbearing and the occurrence of complications, including loosening of osteosynthesis materials. Conclusion: This study demonstrates that there is limited consensus on the rehabilitation for DIACFs. Moreover, it shows that most surgeons are inclined to interpret the current (AO) guideline or their own local protocol freely. New guidelines, supported with well-founded literature, could help surgeons in a more appropriate daily practice in weightbearing for the rehabilitation of calcaneal fractures. [ABSTRACT FROM AUTHOR]

Brick-and-mortar grocery retailers that undertake major format changes often do so in a staggered rollout and radically transform just one store at a time. This approach begs two questions: What effects does a radical store transformation have on existing customers' sales at the transformed store (own-effect) and at the chain's nearby untransformed stores (cross-effect)? Do the effects vary with customer characteristics? These questions are investigated using a quasi-field experiment of a staggered radical store transformation of a German retailer. Conventional wisdom would predict cannibalization of nearby untransformed stores' sales. However, applying our proposed theoretical framework shows, for this empirical case, a negative own- but a positive cross-effect on existing customers. Further, existing customers who had a greater preference for and shopped more at the old format are most likely to migrate. Thus, nearby untransformed stores can help retain existing customers who may get turned off by a radical store transformation. [ABSTRACT FROM AUTHOR]

Negotiations between manufacturers and retailers often go sour. In an attempt to stand their ground, firms increasingly exercise coercive power and decide to delist products until the conflict is resolved. Using an event study, this paper provides knowledge on the performance implications of these so-called conflict delistings. While the results show that, on average, conflict delistings severely damage firm value, the direction and magnitude of the stock market reaction is contingent upon conflict and firm characteristics. Conflict delistings are more harmful to firm value if the focal party is a manufacturer (versus a retailer) or the initiator of the delisting. They also harm firm value more when more brands were delisted and when the size of the focal firm is much larger than the opponent's size. A conflict delisting is more beneficial if the focal party has a strong brand and if the opponent's brand strength is weak. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal diseases, characterized by a treatment-resistant and invasive nature. In line with these inherent aggressive characteristics, only a subset of patients shows a clinical response to the standard of care therapies, thereby highlighting the need for a more personalized treatment approach. In this study, we comprehensively unraveled the intra-patient response heterogeneity and intrinsic aggressive nature of PDAC on bulk and single-organoid resolution. We leveraged a fully characterized PDAC organoid panel (N = 8) and matched our artificial intelligence-driven, live-cell organoid image analysis with retrospective clinical patient response. In line with the clinical outcomes, we identified patient-specific sensitivities to the standard of care therapies (gemcitabine-paclitaxel and FOLFIRINOX) using a growth rate-based and normalized drug response metric. Moreover, the single-organoid analysis was able to detect resistant as well as invasive PDAC organoid clones, which was orchestrates on a patient, therapy, drug, concentration and time-specific level. Furthermore, our in vitro organoid analysis indicated a correlation with the matched patient progression-free survival (PFS) compared to the current, conventional drug response readouts. This work not only provides valuable insights on the response complexity in PDAC, but it also highlights the potential applications (extendable to other tumor types) and clinical translatability of our approach in drug discovery and the emerging era of personalized medicine. [ABSTRACT FROM AUTHOR]

Background: We developed models for tumor segmentation to automate the assessment of total tumor volume (TTV) in patients with colorectal liver metastases (CRLM). Methods: In this prospective cohort study, pre- and post-systemic treatment computed tomography (CT) scans of 259 patients with initially unresectable CRLM of the CAIRO5 trial (NCT02162563) were included. In total, 595 CT scans comprising 8,959 CRLM were divided into training (73%), validation (6.5%), and test sets (21%). Deep learning models were trained with ground truth segmentations of the liver and CRLM. TTV was calculated based on the CRLM segmentations. An external validation cohort was included, comprising 72 preoperative CT scans of patients with 112 resectable CRLM. Image segmentation evaluation metrics and intraclass correlation coefficient (ICC) were calculated. Results: In the test set (122 CT scans), the autosegmentation models showed a global Dice similarity coefficient (DSC) of 0.96 (liver) and 0.86 (CRLM). The corresponding median per-case DSC was 0.96 (interquartile range [IQR] 0.95–0.96) and 0.80 (IQR 0.67–0.87). For tumor segmentation, the intersection-over-union, precision, and recall were 0.75, 0.89, and 0.84, respectively. An excellent agreement was observed between the reference and automatically computed TTV for the test set (ICC 0.98) and external validation cohort (ICC 0.98). In the external validation, the global DSC was 0.82 and the median per-case DSC was 0.60 (IQR 0.29–0.76) for tumor segmentation. Conclusions: Deep learning autosegmentation models were able to segment the liver and CRLM automatically and accurately in patients with initially unresectable CRLM, enabling automatic TTV assessment in such patients. Relevance statement: Automatic segmentation enables the assessment of total tumor volume in patients with colorectal liver metastases, with a high potential of decreasing radiologist's workload and increasing accuracy and consistency. Key points: • Tumor response evaluation is time-consuming, manually performed, and ignores total tumor volume. • Automatic models can accurately segment tumors in patients with colorectal liver metastases. • Total tumor volume can be accurately calculated based on automatic segmentations. [ABSTRACT FROM AUTHOR]

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A large proportion of people living with HIV (PLHIV) in sub-Saharan Africa reside in rural areas. Knowledge of enablers and barriers of adherence to antiretroviral treatment (ART) in these populations is limited. We conducted a cohort study of 501 adult PLHIV on ART at a rural South African treatment facility as a sub-study of a clinical trial (ClinicalTrials.gov NCT03357588). Socio-economic, psychosocial and behavioral characteristics were assessed as covariates of self-reported adherence difficulties, suboptimal pill count adherence and virological failure during 96 weeks of follow-up. Male gender was an independent risk factor for all outcomes. Food insecurity was associated with virological failure in males. Depressive symptoms were independently associated with virological failure in both males and females. Household income and task-oriented coping score were protective against suboptimal pill-count adherence. These results underscore the impact of low household income, food insecurity and depression on outcomes of ART in rural settings and confirm other previously described risk factors. Recognition of these factors and targeted adherence support strategies may improve patient health and treatment outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the efficacy of a novel, multi-active emollient in preventing and managing acute radiation dermatitis (ARD) in breast cancer patients undergoing moderate hypofractionated (HF) radiotherapy (RT) compared to standard of care. Methodsa: A monocentric, open-label, randomized clinical trial (RCT) with breast cancer patients receiving moderate HF (dose: 40.05–55.86 Gy, fractions: 15–21) was conducted between January 2022 and May 2023. The experimental group received the novel emollient, while the control group received the standard skin care. Patients applied the skin care products twice daily during the complete RT course. The primary outcome was the severity of ARD at the final RT session measured by the modified Radiation Therapy Oncology Group (RTOG) criteria. Secondary outcomes included patient symptoms, quality of life (QoL), and treatment satisfaction. Results: A total of 100 patients with 50 patients per group were enrolled. In the control group, 50% of the patients developed RTOG grade 1 ARD and 48% grade 2 or higher, while in the experimental group, the severity of ARD was significantly lower with 82% grade 1 and 16% grade 2 ARD (P =.013, χ2-test). The frequency and severity of xerosis were significantly lower in the experimental compared to the control group (Ps ≤.036, Mann Whiney U test). The impact of ARD on the QoL was low, and treatment satisfaction was high in both groups, with no significant difference. Conclusion: This RCT shows that the novel, multi-active emollient significantly reduced the ARD RTOG grade. Research in a more diverse patient population is warranted. Trial registration: ClinicalTrials.gov: NCT04929808 (11/06/2021). [ABSTRACT FROM AUTHOR]

Childhood adversity is associated with psychopathology. First evidence in adults suggests that threat anticipation, i.e., an enhanced anticipation of unpleasant events creating an enduring sense of threat, may be a putative mechanism linking childhood adversity to psychopathology. This study aimed to test the indirect effect of childhood adversity on psychopathology via threat anticipation in a large community sample of adolescents. We measured childhood trauma and bullying victimization (as indicators of childhood adversity), threat anticipation, general psychopathology and prodromal psychotic symptoms in adolescents aged 12–16 years (full sample size N = 1682; minimum sample size in the complete case sample N = 449) in wave I of the SIGMA study. We found strong evidence that childhood adversity (e.g. childhood trauma, adj. β (aβ) = 0.54, p <.001) and threat anticipation (e.g. aβ = 0.36, p <.001) were associated with general psychopathology and prodromal psychotic symptoms. Moreover, there was evidence that the association between childhood adversity, general psychopathology and prodromal psychotic symptoms is mediated via pathways through threat anticipation (e.g. childhood trauma, aβindirect effect = 0.13, p <.001). Threat anticipation may be a potential mechanism linking childhood adversity and psychopathology in adolescents. [ABSTRACT FROM AUTHOR]

Background: Cosmetic clinics use social media to inform and market to prospective patients. Evidence from social media posts by the UK and Dutch cosmetic clinics illustrates the precarious balance between professionalism and commercialism, and raises important questions for the regulation of these marketing communication efforts. Methods: A random selection of Instagram posts by Dutch and the UK clinics which offer (non-) invasive cosmetic procedures were selected for a qualitative content analysis. The corpus of data comprised 395 posts by six Dutch and four UK clinics, published between January 2018 and July 2019. The method of analysis was inspired by previous qualitative studies into the marketing of cosmetic procedures and can be described as a (discursive) thematic analysis. Results and Conclusions: The tension between the medical-professional and commercial nature of cosmetic procedures was evident in the Instagram posts by Dutch and UK clinics. Despite calls for 'ethical' marketing on social media, this study illustrates that marketing materials are not always in line with current advertising guidelines. Whereas advertising standards authorities have warned against the trivialization of cosmetic procedures, posts by clinics backgrounded the medical nature of procedures in favor of more commercial advertising appeals. Furthermore, the posts demonstrated little diversity in terms of models' gender, ethnicity and body type, which reinforces narrow contemporary beauty ideals. Level of Evidence V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. [ABSTRACT FROM AUTHOR]

Boron-containing materials are efficient catalysts for the oxidative dehydrogenation of propane to propylene, proceeding via radical intermediates. The radical mechanism is initiated by the solid surface and propagated in the gas phase. It has been hypothesized that the propylene selectivity could be increased by enhancing the gas-phase contributions by favoring the formation of iso- over n-propyl radical intermediates. Indeed, whereas n-propyl radicals can be converted to both propylene and ethylene, iso-propyl radicals yield exclusively propylene. In this contribution, we explore 3D printing to structure the hexagonal boron nitride (hBN) heterogeneous catalyst with high void space. 3D-printed hBN monoliths were found to exhibit a higher olefin selectivity and a higher rpropylene/rethylene ratio as compared to traditional pack beds of hBN pellets. Our kinetic studies indicate the increase of reaction order in propane from 1.5 to 2.3, implying the promotion of gas-phase reaction. This work does not only shows that 3D-structured catalysts lead to higher propylene selectivity, it also confirms the hypothesized reaction mechanism and illustrates the power of molecular insights in selective oxidation chemistry to improve the performance. [ABSTRACT FROM AUTHOR]

Background: Consensus on resectability criteria for colorectal cancer liver metastases (CRLM) is lacking, resulting in differences in therapeutic strategies. This study evaluated variability of resectability assessments and local treatment plans for patients with initially unresectable CRLM by the liver expert panel from the randomised phase III CAIRO5 study. Methods: The liver panel, comprising surgeons and radiologists, evaluated resectability by predefined criteria at baseline and 2-monthly thereafter. If surgeons judged CRLM as resectable, detailed local treatment plans were provided. The panel chair determined the conclusion of resectability status and local treatment advice, and forwarded it to local surgeons. Results: A total of 1149 panel evaluations of 496 patients were included. Intersurgeon disagreement was observed in 50% of evaluations and was lower at baseline than follow-up (36% vs. 60%, p < 0.001). Among surgeons in general, votes for resectable CRLM at baseline and follow-up ranged between 0–12% and 27–62%, and for permanently unresectable CRLM between 3–40% and 6–47%, respectively. Surgeons proposed different local treatment plans in 77% of patients. The most pronounced intersurgeon differences concerned the advice to proceed with hemihepatectomy versus parenchymal-preserving approaches. Eighty-four percent of patients judged by the panel as having resectable CRLM indeed received local treatment. Local surgeons followed the technical plan proposed by the panel in 40% of patients. Conclusion: Considerable variability exists among expert liver surgeons in assessing resectability and local treatment planning of initially unresectable CRLM. This stresses the value of panel-based decisions, and the need for consensus guidelines on resectability criteria and technical approach to prevent unwarranted variability in clinical practice. [ABSTRACT FROM AUTHOR]

We present a case series of three patients with a uro-symphyseal fistula (USF), a rare complication after prostate cancer treatment. The etiology mostly consists of a combination of previous surgical treatment for prostate cancer followed by radiotherapy and/or postoperative endoscopic interventions. There should be high index of suspicion for USF if these patients have recurrent urinary tract infections, pubic or perineal pain during mobilization and signs of osteomyelitis. The main work up includes a combination of a urethra-cystoscopy and magnetic resonance imaging (MRI) of the pelvic region. In these case series we show that if conservative therapies fail, patients may be successfully treated by surgical resection of the fistulous tract, urinary diversion and treatment for osteomyelitis. [ABSTRACT FROM AUTHOR]

Objective: The Dutch law on youth care (the Youth Act) was implemented from 2015 onwards. One of the government's aims by implementing this new policy was de-medicalization of youths by separating youth mental healthcare from the rest of the healthcare system. A previous study conducted by our research group showed that prevalence rates of antipsychotic drug prescriptions stabilized among Dutch youth in the period 2005–2015, just before the introduction of the Youth Act. In our study, we aimed to describe antipsychotic drug use among Dutch children aged 0–19 years old before and after implementation of the Youth Act (2010–2019). Methods: We analyzed prescription data of 7405 youths aged 0–19 years using antipsychotic drugs between 2010 and 2019, derived from a large Dutch community pharmacy-based prescription database (IADB.nl). Results: Prevalence rates of antipsychotic drug use per thousand youths decreased significantly in youths aged 7–12 years old in 2019 compared to 2015 (7.9 vs 9.0 p < 0.05). By contrast, prevalence rates increased in adolescent females in 2019 compared to 2015 (11.8 vs 9.5 p < 0.05). Incidence rates increased significantly in adolescent youths in 2019 compared to 2015 (3.9 vs 3.0 p < 0.05), specifically among adolescent girls (4.2 per thousand in 2019 compared to 3.0 per thousand in 2015). Dosages in milligram declined for the most commonly prescribed antipsychotic drugs during the study period. The mean duration of antipsychotic drug use in the study period was 5.7 (95% CI 5.2–6.2) months. Conclusion: Despite the aim of the Youth Act to achieve de-medicalization of youths, no clear reduction was observed in prevalence rates of antipsychotic drugs or treatment duration in all subgroups. Prevalence rates even increased in adolescent females. [ABSTRACT FROM AUTHOR]

Background: Depression is characterized by different forms of overgeneralization that are all assumed to play a causal role in the development and course of depression. Methods: We examined, in a community sample of over 625 individuals, whether these different forms of overgeneralization are correlated and whether they are prospective predictors of depression at 6-month follow-up. Results: Negative overgeneralization to the self and across situations—two types of overgeneralized thinking processes—were significantly but weakly related, but neither of them was related to overgeneral memory—a memory-based form of overgeneralization. Overgeneralization to the self and overgeneral memory both predicted depression symptoms at follow-up. Further, two and three-way interactions indicated that higher levels of overgeneralization processes interact to predict depressive symptoms. Overgeneralization to the self and overgeneral memory both independently predicted probable recurrence of a major depressive episode during the follow-up period in individuals that formerly experienced depression. Conclusions: Findings suggest that overgeneralization in depression is not a unitary construct and that different overgeneralization processes play independent and interacting roles in the course of depression. [ABSTRACT FROM AUTHOR]

Angiogenesis, barriergenesis, and immune cell migration are all key physiological events that are dependent on the functional characteristics of the vascular endothelium. The protein family of Nectins and Nectin-like molecules (Necls) is a group of cell adhesion molecules that are widely expressed by different endothelial cell types. The family includes four Nectins (Nectin-1 to -4) and five Necls (Necl-1 to -5) that either interact with each other by forming homo- and heterotypical interactions or bind to ligands expressed within the immune system. Nectin and Necl proteins are mainly described to play a role in cancer immunology and in the development of the nervous system. However, Nectins and Necls are underestimated players in the formation of blood vessels, their barrier properties, and in guiding transendothelial migration of leukocytes. This review summarizes their role in supporting the endothelial barrier through their function in angiogenesis, cell–cell junction formation, and immune cell migration. In addition, this review provides a detailed overview of the expression patterns of Nectins and Necls in the vascular endothelium. [ABSTRACT FROM AUTHOR]